A variety of diverse pharmacologically active alkaloids have been isolated from skin extracts of dendrobatid frogs and their structures and pharmacology investigated. These include gephyrotoxin, a novel tricyclic alkaloid with marked activity as a muscarinic antagonist; pumiliotoxin A and B, complex alkaloids with pronounced cardiotonic activity; and finally an alkaloid of unknown structure with potent analgesic activity. Radioactive perhydrohistrionicotoxin did not bind at the acetylcholine receptor purified from the electroplax of the electric ray, but did bind with high affinity to an associated but separable ion conductance modulator. Interaction of batrachotoxin with the sodium channel in innervated cells of the electroplax of electric eel required membrane depolarization. Dihydroisohistrionicotoxin altered binding of agonists and antagonists to acetylcholine receptors in cultured neuroma cells and cultured skeletal muscle cells. In muscle cells the toxin appears to bind to an allosteric effector site, thereby desensitizing the channel and altering the acetylcholine-receptor site. BIBLIOGRAPHIC REFERENCES: Bartels-Bernal, E., Rosenberry, T.L., and Daly,J.W.: Effect of batrachotoxin on the electroplax of electric eel: Evidence for voltage-dependent interaction with sodium channels. Proc. Natl. Acad. Sci. USA. 74: 951-955, 1977. Daly, J.W., Witkop, B., Tokuyama, T., Nishikawa, T., and Karle, I.L.: Gephyrotoxins, Histrionicotoxins, and pumiliotoxins from the neotropical frog Dendrobates histrionicus. Helv. Chim. Acta 60: 1128-1140, 1977.